Vitamin E, which is known by many alternative appellations (including tocopherol), is required by all animals, including those as diverse in physiology and environment as humans and fish, for example. As used in many applications, and as used herein, the terms "Vitamin E" or "tocopherol" are used to mean any mixture of physiologically active tocopherols, including Vitamin E acetates and other prodrugs of Vitamin E, as well as tocopherol derivatives, which include Vitamin K.sub.1 -chromanol and Vitamin K.sub.1 -chromenol. Natural .alpha.-tocopherol, one of the more common tocopherols, is usually found with beta-, gamma- and delta-tocopherols. (See, e.g., The Merck Index, 10th ed., Merck & Co., Inc., 1983, at page 1437.)
In general, dietary requirements range from about 3 to about 70 IU (international units) per kilogram of dietary intake in animals. (See, e.g., Machlin, L.J., ed., Handbook of Vitamins, Marcel Dekker, Inc., 1983, particularly Chapter 3, "Vitamin E".) Vitamin E is widely distributed in nature, with the more common dietary sources being meats, dairy products, eggs, and vegetable oils.
Natural Vitamin E encompasses a family of compounds and isomers, all of which are phenolic isoprenoid derivatives. Of these compounds, D-.alpha.-tocopherol is the most abundant and has the highest biological activity. Many commercial products are synthetically produced and are based on the racemic mixture DL-.alpha.-tocopherol. DL-.alpha.-tocopherol acetate is a common commercial form, and its biological activity is expressed as 1.00 IU per milligram (mg). The biological activity of tocopherol ester is almost equivalent to that of tocopherol, to which it is rapidly hydrolyzed after ingestion. Other examples of prodrug derivatives are tocopheryl succinate, tocopheryl nicotinate and tocopheryl phosphate.
Vitamin E shows an abundant variety of beneficial biological activities which have been explored and studied since about 1925, and many new applications remain to be described. We have now discovered and shown for the first time that Vitamin E has substantial antiviral activity. In particular, we have found that the antiviral activity of Vitamin E is demonstrated by its protective effect against HIV-1 infection, as illustrated in a model using Molt-3 cells.
It is well known that diseases associated with viral and retroviral infections are major medical, veterinary and agricultural problems in the United States and worldwide. Diseases of known viral origin include chicken pox, the common cold, cytomegalovirus disease (CMV), dengue fever, encephalitis, hoof-and-mouth disease, herpes infections, influenza, keratoconjunctivitis, measles, mumps, Newcastle disease, poliomyelitis, rabies, rubella, scrapie, shingles, smallpox, tick fever, West Nile Fever, and yellow fever, to name but a few. An especially serious problem at the present time is the rapid escalation in reported cases of AIDS (Acquired Immune Deficiency Syndrome), whose causative agent is strongly suspected to be HIV (Human Immunodeficiency Virus).
There are urgent and compelling reasons for the development of more efficacious and safer treatments of viral and retroviral infections. It is estimated that at least one and a half million people in the United States alone have been infected with the human immunodeficiency (HIV) or AIDS virus. HIV causes a decay of a major arm of the immune system, the immune helper cells (T4 helper or CD4.sup.+ helper cells). This decay leads to a wide spectrum of diseases, generally called HIV disease, of which AIDS is the most serious and devastating form. It is anticipated that over one third of the budget for medical care in the U.S. will be consumed on HIV disease. There is an escalating incidence of other viral diseases as well. For example, cytomegalovirus (CMV) infection is rapidly increasing in the teenage population of the United States.
Therefore, in response to this pervasive need for safer and more efficacious treatments of viral and retroviral infections, we now describe our findings and propose compositions and methods for treatment of viral and retroviral infections using Vitamin E-based compositions.